Neither rituximab (Rituxan) nor abatacept (Orencia) improved any primary or secondary endpoint, reported Joan T. Merrill, M.D., of the University of Oklahoma in Oklahoma City, and colleagues at the American College of Rheumatology meeting.

Only aspirin, antimalarial drugs, and prednisone (Deltasone) have won FDA approval for lupus, which is notoriously difficult to treat. Given the lack of options, "the standard of care in lupus is continuously off-label," Dr. Merrill said. "People have no choice."

Indeed, an informal survey she took of the audience at the late-breaking trials session revealed that a fair number of rheumatologists have tried rituximab for their lupus patients, and none was willing to stop on the basis of the data she presented.

Jeffrey Lawson, M.D., of the Piedmont Arthritis Clinic in Greenville, S.C., said in an interview afterward that he was not at all convinced by the data.

Despite the lack of evidence and expense of biologics, frustration makes these treatments attractive, said Dr. Lawson, who was not involved in the studies.

Rituximab has a feasible mechanism in lupus by depleting B-cells, which have been posited as playing a central role in the condition, Dr. Merrill noted.

All 257 participants were on a stable dose of one immunosuppressive drug -- methotrexate, mycophenolate mofetil (CellCept), or azathioprine (Azasan, Imuran).

Most were already chronic prednisone users but all were randomized to a dose of 0.5, 0.75, or 1.0 mg prednisone, which was tapered off during the study.

For the primary endpoint, the proportion of patients who had a major clinical response defined as no severe flare up to week 24 and no moderate or severe flare to week 52 was similar between groups (12.4% rituximab versus 15.9% placebo) as was the proportion who had a partial clinical response (17.2% versus 12.5%).

None of the secondary endpoints for British Isles Lupus Assessment (BILAG) scores or SF-36 physical component scores or reduction in steroid doses was significant either.

But an exploratory endpoint -- mean BILAG global score -- offered a possible explanation. For this endpoint, an identical improvement was seen in the first weeks of treatment for both groups that remained fairly stable thereafter.

"This confirms what we have all hypothesized for a very long time," Dr. Merrill noted. "Steroids work."

Maintenance of background medications plus prednisone was apparently sufficient to keep that improvement stable over the course of the trial and "really not giving any other treatment a chance," she said.

In the subgroup analyses, African Americans and Hispanics did significantly better on rituximab than placebo with a higher proportion meeting the high bar for major or partial clinical response.

Methotrexate-treated patients also did significantly better with rituximab (P=0.007).

Serious adverse event rates were similar between groups, although rituximab was associated with a small trend for more neutropenia and more frequent non-serious infections and infusion reactions on the second course.

The researchers found a similar lack of benefit in the first trial of abatacept for SLE.

This one-year, phase II trial included 175 patients with lupus and active polyarthritis, serositis, or discoid lesions who were randomized to infusions of abatacept (about 10 mg/kg) or placebo on days one, 15, 29, then every four weeks.

Again, patients were given prednisone tapered off after one month at 30 mg per day.

For the primary endpoint, abatacept-treated patients were no less likely to have a new flare adjudicated as meeting BILAG A or B criteria after the start of the steroid taper (79.7% versus 82.5%, difference -3.5, 95% confidence interval -15.3 to 8.3).

Likewise, secondary endpoints using less stringent cutpoints for flares were not significantly different between groups.

Notably, new flares as assessed by the treating physician without use of BILAG scale scoring were significantly reduced as well, which highlighted concerns about trial design.

"I think the accuracy of the measurements is a problem," Dr. Lawson said.

Dr. Merrill defended BILAG as a sensitive tool that would have picked up a difference if there had been one, but she agreed with audience comments during the question-and-answer session that the best cutoffs to use in trials needs further work.

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